Memory impairments constitute a major problem in society. These occur naturally with aging and as a result of diseases (e.g., Alzheimer's disease), and are exacerbated by stress. The hippocampus, as part of a brain system necessary for the formation of stable declarative (or explicit) memory appears to be prominently susceptible to uncontrollable stress. Recent rodent studies demonstrate that stress interferes with learning of hippocarnpal-dependent spatial memory and alters the inducibility of long-term potentiation (LTP) and long-term depression (LTD)--two putative synaptic mechanisms of information storage-in the hippocampus. Other studies indicate that the amygdala is critically involved in coordinating stress-related behaviors and modulating hippocampal functioning. Our long-term goal is to understand the amygdalar mechanisms involved in mediating stress effects on hippocampal functioning.There are three specific aims of the project: (1) an IN VITRO ANALYSIS will investigate the role of the amygdala in mediating stress effects on hippocampal LTP/LTD; (2) a BEHAVIORAL ANALYSIS will examine the amygdalar mechanisms mediating stress-induced impairments in hippocampal-dependent spatial memory; and (3) a SINGLE UNIT ANALYSIS of hippocampal place cells will integrate stress effects on hippocampal plasticity and spatial memory. These related aims are designed to test our current working hypothesis that stress-induced alterations in hippocampal functioning are due to excessive activity exerted by the amygdala onto the hippocampus during stress.Data obtained from this project would be of significance (1) from a basic scientific perspective providing valuable information concerning how hippocampal plasticity might be regulated by naturalistic factors (such as stress) and the underlying mechanisms subserving stress effects on hippocampal functioning; and (2) from an applied perspective, providing important insights that will assist in developing therapeutic approaches to alleviate cognitive impairments associated with stress-induced ailments (such as anxiety, posttraumatic stress disorder, vascular dementia) that severely limit the quality of human life.